258 research outputs found
Non3 is an essential Drosophila gene required for proper nucleolus assembly
The nucleolus is a dynamic non-membrane-bound nuclear organelle, which plays key roles not only in ribosome biogenesis but also in many other cellular processes. Consistent with its multiple functions, the nucleolus has been implicated in many human diseases, including cancer and degenerative pathologies of the nervous system and heart. Here, we report the characterization of the Drosophila Non3 (Novel nucleolar protein 3) gene, which encodes a protein homologous to the human Brix domain-containing Rpf2 that has been shown to control ribosomal RNA (rRNA) processing. We used imprecise P-element excision to generate four new mutant alleles in the Non3 gene. Complementation and phenotypic analyses showed that these Non3 mutations can be arranged in an allelic series that includes both viable and lethal alleles. The strongest lethal allele (Non3∆600) is a genetically null allele that carries a large deletion of the gene and exhibits early lethality when homozygous. Flies heterozygous for Non3∆600 occasionally exhibit a mild reduction in the bristle size, but develop normally and are fertile. However, heteroallelic combinations of viable Non3 mutations (Non3197, Non3310 and Non3259) display a Minute-like phenotype, consisting in delayed development and short and thin bristles, suggesting that they are defective in ribosome biogenesis. We also demonstrate that the Non3 protein localizes to the nucleolus of larval brain cells and it is required for proper nucleolar localization of Fibrillarin, a protein important for post-translational modification and processing of rRNAs. In summary, we generated a number of genetic and biochemical tools that were exploited for an initial characterization of Non3, and will be instrumental for future functional studies on this gene and its protein product
Moonlighting in Mitosis: Analysis of the Mitotic Functions of Transcription and Splicing Factors
Moonlighting proteins can perform one or more additional functions besides their primary role. It has been posited that a protein can acquire a moonlighting function through a gradual evolutionary process, which is favored when the primary and secondary functions are exerted in different cellular compartments. Transcription factors (TFs) and splicing factors (SFs) control processes that occur in interphase nuclei and are strongly reduced during cell division, and are therefore in a favorable situation to evolve moonlighting mitotic functions. However, recently published moonlighting protein databases, which comprise almost 400 proteins, do not include TFs and SFs with secondary mitotic functions. We searched the literature and found several TFs and SFs with bona fide moonlighting mitotic functions, namely they localize to specific mitotic structure(s), interact with proteins enriched in the same structure(s), and are required for proper morphology and functioning of the structure(s). In addition, we describe TFs and SFs that localize to mitotic structures but cannot be classified as moonlighting proteins due to insufficient data on their biochemical interactions and mitotic roles. Nevertheless, we hypothesize that most TFs and SFs with specific mitotic localizations have either minor or redundant moonlighting functions, or are evolving towards the acquisition of these functions
Moonlighting in mitosis:Analysis of the mitotic functions of transcription and splicing factors
Moonlighting proteins can perform one or more additional functions besides their primary role. It has been posited that a protein can acquire a moonlighting function through a gradual evolutionary process, which is favored when the primary and secondary functions are exerted in different cellular compartments. Transcription factors (TFs) and splicing factors (SFs) control processes that occur in interphase nuclei and are strongly reduced during cell division, and are therefore in a favorable situation to evolve moonlighting mitotic functions. However, recently published moonlighting protein databases, which comprise almost 400 proteins, do not include TFs and SFs with secondary mitotic functions. We searched the literature and found several TFs and SFs with bona fide moonlighting mitotic functions, namely they localize to specific mitotic structure(s), interact with proteins enriched in the same structure(s), and are required for proper morphology and functioning of the structure(s). In addition, we describe TFs and SFs that localize to mitotic structures but cannot be classified as moonlighting proteins due to insufficient data on their biochemical interactions and mitotic roles. Nevertheless, we hypothesize that most TFs and SFs with specific mitotic localizations have either minor or redundant moonlighting functions, or are evolving towards the acquisition of these functions
Влияние мексидола на состав и перекисное окисление липидов миокарда в постреанимационном периоде
An experimental model of clinical death followed by reperfusion was used to study the postresuscitative effects of the anti-hypoxant mexidole on lipid composition and peroxidation rates in the rat myocardium. The use of mexidole in early reperfusion was shown to lead to the altered phospholipid composition of cardiomyocytes, the normalization of the activities of superoxide dismutase and catalase, the lower levels of malonic dialdehyde on postresuscitative day 30. Modifications of the myocardium lipid spectrum appeared as the elevated levels of phosphatidylserine and phosphatidylethanolamine that maintained intracellular ionic homeostasis and myocardial performance, as well as decreases in lysophosphatidylcholine having proarrhythmic activity and in sphingomyelin and phosphatidic acids.На экспериментальной модели клинической смерти с последующей реперфузией исследовано влияние антигипок-санта метаболического типа — мексидола на липидный состав и активность перекисного окисления липидов ткани сердца крыс в отдаленном постреанимационном периоде. Показано, что применение мексидола в раннем реперфу-зионном периоде приводило к изменению фосфолипидного состава кардиомиоцитов, нормализации активности су-пероксиддисмутазы и каталазы, снижению содержания малонового диальдегида на 30-е сутки постреанимационного периода. Модификации спектра липидов ткани сердца проявлялись увеличением содержания фосфатидилсерина, фосфатидилэтаноламина, обеспечивающих поддержание внутриклеточного ионного гомеостаза и деятельности сердечной мышцы, уменьшением лизофосфатидилхолина, обладающего аритмогенным действием, сфингомиелина и фосфатидных кислот
БОЛЕЗНЬ ЛЕБЕРА. КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ
Violation of visual functions and oculomotor frustration develop at 90% of patients with MS. More than a half of patients are transferred by the numerous recurrence of an optical neuritis which is coming to an end with a partial atrophy of optic nerve. For well-timed purpose of pathogenetic treatment differential diagnostics with other diseases, being accompanied an atrophy of an optic nerve, in particular with Leber's disease. Нарушение зрительных функций и глазодвигательные расстройства развиваются у 90% больных с рассеянным склерозом. Более половины больных переносят неоднократные рецидивы оптического неврита, заканчивающиеся частичной атрофией зрительного нерва. Для своевременного назначения патогенетического лечения чрезвычайно важным является дифференциальная диагностика с другими заболеваниями, сопровождающимися атрофией зрительного нерва, в частности с болезнью Лебера.
Отдаленные результаты эмболизации артериовенозных мальформаций головного мозга гистоакрилом
N-butyl cyanoacrylate (Hystoacryl) is one of the most frequently used glues for the treatment of cerebral arteriovenous malformation. However, long-term results of its treatment with Hystoacryl are insufficiently studied. 136 patients were examined. Catamnesis was (4 ± 1) year. The quality of life is reduced due to cognitive and motor disorders.В последнее время наиболее распространенным эмболизирующим веществом является смесь гистоакрила с липиодолом. При этом в системе комплексного лечения артериовенозных мальформаций отдаленные результаты эмболизации изучены недостаточно. Проведено обследование 136 пациентов со средним сроком катамнеза (4 ± 1) год. Установлено, что снижение качества жизни пациентов обусловлено когнитивными, двигательными нарушениями
Значимость экспрессии онкопротеина Her-2/neu и компонента межклеточного матрикса тенасцина для метастатической активности рака мочевого пузыря
The authors conducted an immunohistochemical study with antibodies to Her-2/neu and tenascin in urothelial bladder carcinoma. The samples taken from 32 patients with stages Т2b/T3a, N0 and N+ urinary bladder carcinoma were studied. The tumor cells showed hyper-expression of the oncoprotein Her-2/neu in 6 out of 13 patients with metastases to the regional lymph nodes (T3b и T3a) and in 2 out of 7 tumors (Т3а) without lymph node involvement. Quantitative assessment of the reaction with tenascin antibodies revealed that in the metastatic lymph node involvement group, the staining area was much larger than that in metastasis-free group and it averaged 49.83 and 44.21% and 11.27 and 15.7%, respectively. Comparison analysis of Her-2/neu and tenascin expression revealed no clinically significant regularities. The study of the intercellular matrix showed a high correlation between the increase in the share of tenascin-expressing and/or containing structures and the rise in the metastatic activity of a tumor.
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